Population Dynamics and Structural Effects at Short and Long Range Support the Hypothesis of the Selective Advantage of the G614 SARS-CoV-2 Spike Variant
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Abstract
SARS-CoV-2 epidemics quickly propagated worldwide, sorting virus genomic variants in newly established propagules of infections. Stochasticity in transmission within and between countries or an actual selective advantage could explain the global high frequency reached by some genomic variants. Using statistical analyses, demographic reconstructions, and molecular dynamics simulations, we show that the globally invasive G614 spike variant 1) underwent a significant demographic expansion in most countries explained neither by stochastic effects nor by overrepresentation in clinical samples, 2) increases the spike S1/S2 furin-like site conformational plasticity (short-range effect), and 3) modifies the internal motion of the receptor-binding domain affecting its cross-connection with other functional domains (long-range effect). Our results support the hypothesis of a selective advantage at the basis of the spread of the G614 variant, which we suggest may be due to structural modification of the spike protein at the S1/S2 proteolytic site, and provide structural information to guide the design of variant-specific drugs.
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SciScore for 10.1101/2020.05.14.095620: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Alignment was checked by eye in Aliview (Larsson 2014) to remove indels, and then parsed using a custom python script to trim sequences before position 150 and after position 29150, and discard sequences with more than 500 missing bases. pythonsuggested: (IPython, RRID:SCR_001658)The demographic history of the D/G614 SARS-CoV-2 variants in each territory was reconstructed using the Bayesian Skyline plot analyses as implemented in Beast v2.6 (Bouckaert et al 2019). Beastsuggested: (BEAST, RRID:SCR_010228)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: …SciScore for 10.1101/2020.05.14.095620: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Alignment was checked by eye in Aliview (Larsson 2014) to remove indels, and then parsed using a custom python script to trim sequences before position 150 and after position 29150, and discard sequences with more than 500 missing bases. pythonsuggested: (IPython, RRID:SCR_001658)The demographic history of the D/G614 SARS-CoV-2 variants in each territory was reconstructed using the Bayesian Skyline plot analyses as implemented in Beast v2.6 (Bouckaert et al 2019). Beastsuggested: (BEAST, RRID:SCR_010228)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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